Search PubMed⌕ Search

Biomedical subjects

M Klockars

Publications and source records attributed to M Klockars.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pleural fluid interferon-gamma and tumour necrosis factor-alpha in tuberculous and rheumatoid pleurisy.

Tuberculous and rheumatoid pleural effusions show features suggesting a strong local cellular immune response. Pleural fluid (Pf) from patients with tuberculosis, rheumatoid arthritis (RA) and other diseases were compared with respect to interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Immunoassays were used to determine Pf-IFN-gamma and Pf-TNF-alpha in 102 patients, including 11 with RA, 31 with verified tuberculosis, 23 with suspected tuberculosis, 11 with pneumonia, 14 with lung cancer and 12 with congestive heart failure. Measurable Pf-IFN-gamma occurred exclusively in patients with verified (median 1.8 ng x mL-1; 95% confidence interval (95% CI) 0.63-4.0 ng x mL-1) or suspected (0.37 ng x mL-1; 95%CI 0-0.7 ng x mL-1) tuberculosis. The highest median Pf-IFN-gamma was observed in those patients who showed a positive pleural fluid culture for Mycobacterium tuberculosis. In pleural effusions due to other diseases, including RA, IFN-gamma was undetectable. The highest Pf-TNF-alpha occurred in verified tuberculosis (median 198 ng x L-1; 95% CI 169-222 ng x L-1) and RA (210 ng x L-1; 95% CI 147-231 ng x L-1). Pleural fluid interferon-gamma is a highly useful marker for diagnosing tuberculous pleurisy. Although tuberculous and rheumatoid pleural effusions share several biochemical features, they are strikingly different with respect to interferon-gamma.

Arthritis, Rheumatoid↗
PubMed1995

Different contributions of cytochrome P450 2E1 and P450 2B1/2 to chloroform hepatotoxicity in rat.

The contribution of cytochrome P450 isozymes CYP2E1 and CYP2B1/2 to chloroform-induced hepatotoxicity taken at 18 hr after the treatment was investigated in rats treated with n-hexane as an inducer of CYP2E1, 2-hexanone as an inducer of CYP2E1 and CYP2B1/2, and phenobarbital (PB) as an inducer of CYP2B1/2. Hepatic damage was evaluated by gross measurement of plasma alanine aminotransferase activity and histopathological examination. All treatments potentiated chloroform-induced hepatic damage. In n-hexane-pretreated rats, the damage was maximal with the middle dose of chloroform (0.2 ml/kg), whereas the damage increased with dose in rats treated with 2-hexanone or PB. The degree of hepatic damage induced with the three pretreatments was in the following order: n-hexane > 2-hexanone = PB with the middle dose of chloroform and PB >> 2-hexanone > n-hexane with the high dose (0.5 ml/kg); little difference among the pretreatments was seen with the low dose (0.1 ml/kg). These findings suggest that CYP2E1 is a low Km isoform and CYP2B1/2 a high Km isoform for chloroform activation. CYP2E1-dependent hepatic damage was characterized by ballooned hepatocytes, which were restricted to the centrilobular area; with CYP2B1/2, more necrotic than ballooned hepatocytes were seen and the necrotic hepatocytes were found not only in the centrilobular but also in the midzonal and periportal areas. Chloroform treatment did not affect the activity of N-nitrosodimethylamine N-demethylase in pretreated rats; the high dose increased the activity in control rats. In contrast, the high dose of chloroform decreased the activity of 7-pentoxyresorufin O-depentylase in all induced rats but not in controls. Immunoinhibition and immunoblot analyses showed that the high dose of chloroform induced CYP2E1 in control rats but decreased CYP2B1/2 in all pretreated rats. These results suggest that although both CYP2E1 and CYP2B1/2 contribute to chloroform-induced hepatic damage, they do so quite differently.

Alanine Transaminase↗
PubMed1995

Neutrophil and asbestos fiber-induced cytotoxicity in cultured human mesothelial and bronchial epithelial cells.

This study investigates reactive oxygen species generation and oxidant-related cytotoxicity induced by amosite asbestos fibers and polymorphonuclear leucocytes (PMNs) in human mesothelial cells and human bronchial epithelial cells in vitro. Transformed human pleural mesothelial cells (MET 5A) and bronchial epithelial cells (BEAS 2B) were treated with amosite (2 micrograms/cm2) for 48 h. After 24 h of incubation, the cells were exposed for 1 h to nonactivated or amosite (50 micrograms) activated PMNs, washed, and incubated for another 23 h. Reactive oxygen species generation by the PMNs and the target cells was measured by chemiluminescence. Cell injury was assessed by cellular adenine nucleotide depletion, extracellular release of nucleotides, and lactate dehydrogenase (LDH). Amosite-activated (but also to a lesser degree nonactivated) PMNs released substantial amounts of reactive oxygen metabolites, whereas the chemiluminescence of amosite-exposed mesothelial cells and epithelial cells did not differ from the background. Amosite treatment (48 h) of the target cells did not change intracellular adenine nucleotides (ATP, ADP, AMP) or nucleotide catabolite products (xanthine, hypoxanthine, and uric acid). When the target cells were exposed to nonactivated PMNs, significant adenine nucleotide depletion and nucleotide catabolite accumulation was observed in mesothelial cells only. In separate experiments, when the target cells were exposed to amosite-activated PMNs, the target cell injury was further potentiated compared with the amosite treatment alone or exposure to nonactivated PMNs. In conclusion, this study suggests the importance of inflammatory cell-derived free radicals in the development of amosite-induced mesothelial cell injury.

Adenine Nucleotides↗
PubMed1994

Bacillus Calmette-Guérin (BCG) and immunoglobulins synergistically enhance mineral dust-induced production of reactive oxygen metabolites by human monocytes.

The modulating effect of BCG and polyclonal immunoglobulin on mineral dust-induced production of reactive oxygen metabolites (ROM) by human monocytes was studied using luminol-dependent chemiluminescence. BCG and immunoglobulin synergistically amplified the ROM production induced by chrysotile asbestos and quartz particles, and BCG caused a sharper dose response for poly-immunoglobulin added to the mineral dusts. Immunoglobulins did not affect zymosan yeast-induced ROM production, which was enhanced strongly by BCG. As there is evidence that phagocyte-derived ROM are of importance in mineral dust-induced lung injury, we suggest that the observed synergism between host response inflammatory mediators (poly-immunoglobulin) and exogenic irritants (BCG) may contribute to the outcome of exposure of mineral dusts, and thus in part explain the individual variations in susceptibility to mineral dust-induced diseases.

Asbestos↗
PubMed1994

Silica dust exposure and lung cancer.

OBJECTIVE: The study evaluated the possibility of a direct association between silica dust exposure and lung cancer. METHODS: Mortality and morbidity among 1026 granite workers was followed in 1940-1989. Regional census data for 1970-1985 and lung cancer incidence data were also linked. The cytotoxicity of different granite fractions and their capacity to induce reactive oxygen species (ROS) in human leukocytes was studied in vitro. RESULTS: Excess lung cancer mortality was found during several follow-up periods. The rate ratios were 1.6-3.8 for different latency periods. Lung cancer risk increased with the length of exposure and latency. Lung cancer morbidity in 1953-1987 showed an excess for the red and grey granite areas, the rate ratio being 2.5 for > or = 20-year latency. Only one lung cancer case came from the black granite area. The cancer cases from the grey area had a shorter latency than those from the red area. The mineral composition differed for each area. The strongest ROS-inducing activity of grey and red granite was seen in the quartz-containing fractions. In the cytotoxicity tests the quartz-containing fractions of the grey and red granite also caused the strongest lactic dehydrogenase (LDH) release. However, plagioclase, the main constituent of black granite (60%), had approximately the same ability to induce ROS as the quartz-containing fractions of red and grey granite. CONCLUSIONS: The cancer morbidity and mortality figures of the three different granite areas, combined with the found differences in biological activity of granite dusts and a hypothesis that there is a cancer-inducing mechanism for ROS, point to a direct role for quartz in cancer induction.

Adult↗
PubMed1994

Pleural fluid soluble interleukin 2 receptor in rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: To study local cellular immune reactions in the pleural fluid of patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Using an immunoenzymometric assay, the concentration of soluble interleukin 2 receptor (sIL-2R) was measured in the pleural fluid of 13 patients with RA, 6 patients with SLE and 72 patients with pleural effusions of other etiologies, including tuberculosis, cancer, pneumonia and congestive heart failure. RESULTS: The mean pleural fluid sIL-2R concentration was significantly higher in patients with RA (593 pM, range 252-1558) than in patients with SLE (145 pM, range 94-236; p < 0.005), cancer (224 pM, range 98-521, p < 0.01), pneumonia (177 pM, range 60-343, p < 0.005) and congestive heart failure (139 pM, range 56-228, p < 0.005), but as high in patients with tuberculous pleurisy (mean 390 pM, range 151-512). The highest mean pleural fluid to serum sIL-2R ratios were observed in patients with RA and with tuberculosis. CONCLUSION: Measurement of sIL-2R in pleural fluid is useful for the differentiation of pleural effusions in RA from those occurring in SLE. High levels of sIL-2R associated with a local T cell mediated immune reaction may serve an immunoregulatory purpose in rheumatoid pleurisy.

Adolescent↗
PubMed1993

High concentrations of eosinophil cationic protein and eosinophil protein X in eosinophilic pleural effusions.

To analyze the association of the eosinophil granulocyte with pleural effusions, we measured the concentrations of two eosinophil proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), in pleural fluid and serum of 92 patients with pleural effusions of various causes. We observed significantly higher ECP and EPX concentrations in eosinophilic than in noneosinophilic pleural effusions (p < 0.001 and p < 0.05, respectively) and a positive correlation between the concentrations of both eosinophil proteins in pleural fluid and the total number of eosinophils in pleural fluid (ECP: r = 0.66, p < 0.0001; and EPX: r = 0.62, p < 0.0001). There was a positive correlation between the concentrations of ECP in pleural fluid and serum (r = 0.74, p < 0.0001) and between the concentrations of EPX in pleural fluid and serum (r = 0.41, p < 0.001). High ECP and EPX concentrations in pleural fluid indicated nonspecific etiology and not tuberculosis as the cause of the effusion. Our results suggest that eosinophils in pleural effusions release eosinophil proteins and probably actively participate in the local inflammatory reaction.

Blood Proteins↗
PubMed1992

Tumour necrosis factor enhances the asbestos-induced production of reactive oxygen metabolites by human polymorphonuclear leucocytes (PMN).

We studied the effect of recombinant tumour necrosis factor-alpha (TNF-alpha) on the production of reactive oxygen metabolites (ROM) by human PMN exposed in vitro to chrysotile and crocidolite asbestos fibres, quartz dusts and opsonized zymosan. TNF caused a significant increase in ROM release by PMN, and significantly and dose-dependently amplified the ROM production induced by asbestos fibres. The amplification of ROM production by TNF can be of crucial importance in the process of lung inflammation and fibrogenesis in pneumoconioses.

Asbestos↗
PubMed1991

Interferon-gamma and immunoglobulin enhance mineral dust-induced production of reactive oxygen metabolites by human macrophages.

The modulating effect of interferon-gamma (IFN-gamma) and polyclonal immunoglobulin (poly-Ig) on mineral dust-induced production of reactive oxygen metabolites (ROM) by human monocyte-derived macrophages was investigated using lucigenin-dependent chemiluminescence. Activation of the cell cultures with IFN-gamma enhanced the subsequent quartz- and asbestos-induced production of ROM, while the addition of poly-Ig only stimulated chrysotile asbestos-induced ROM production. The combination of IFN activation and the addition of poly-Ig to the reactions caused a 20-fold enhancement of the responses to chrysotile. As increased levels of IFN-gamma and immunoglobulins have been observed in patients with mineral dust-induced diseases, we suggest that "immunological activation" caused by, for example, autoimmune diseases or recurrent pulmonary infections might amplify the production of potentially tissue-injuring ROM by mononuclear phagocytes and may possibly determine the individual susceptibility to mineral dust-related disorders.

Asbestos↗
PubMed1991

Serum adenosine deaminase in viral and bacterial pneumonia.

We measured the activity of serum adenosine deaminase (ADA) in paired sera from 171 military conscripts with radiographically verified pneumonia. Patient serum samples were selected on the basis of serologic analyses identifying as single etiologic agents Streptococcus pneumoniae in 29 patients, Haemophilus influenzae in 7, Mycoplasma pneumoniae in 43, adenovirus in 24, influenza A or B in 12, and parainfluenza in 5 patients. In 14 patients Neisseria meningitidis and in 31 Chlamydia spp were considered the main etiologic agent. Compared with a control group of 45 healthy men, the ADA activity in patients with pneumonia was significantly higher (p less than 0.001) in all patient groups except those with meningococcal pneumonia. The highest ADA levels were seen in patients with pneumonia caused by M pneumoniae (27.4 +/- 9.7 U/L), Chlamydia spp (26.3 +/- 9.1 U/L), and adenovirus (28.5 +/- 10.9 U/L) compared with the controls (11.1 +/- 3.0 U/L). In patients with meningococcal pneumonia, the ADA activity was significantly decreased (p less than 0.001). Serum ADA activity probably reflects differences in cellular immune response to different infectious agents. The ADA determinations may give corroborative information on the etiologic agent of pneumonia.

Adenosine Deaminase↗
PubMed1991

Diagnostic value of cerebrospinal fluid adenosine deaminase determination.

We measured the activity of adenosine deaminase (ADA) in the cerebrospinal fluid of 3 patients with tuberculous meningitis, 38 with viral meningitis, 15 with bacterial meningitis, 5 with malignant lymphoma, 11 with cerebrovascular diseases and 13 with miscellaneous neurological disorders. The highest ADA activities were observed in patients with tuberculous meningitis (median 21.3 U/l, range 20.0-23.0) and lymphoma (13.0 U/l, range 4.0-25.0). The sensitivity of the test for diagnosing tuberculous meningitis was 100% and the specificity 99% when a cut-off value of 20.0 U/l was used. We conclude that determination of ADA in cerebrospinal fluid is useful for the diagnosis of tuberculous meningitis, but that high activity also can be seen in some other CNS disorders, e.g. lymphoma with meningeal involvement.

Adenosine Deaminase↗
PubMed1991

Work load and individual factors affecting work ability among aging municipal employees.

The effects of work stressors, individual characteristics, symptoms, and diseases on work ability were studied among 4255 municipal employees. Work ability was assessed by a work ability index in two cross-sectional inquiries, one in 1981 and the other in 1985. The most impairing for work ability were mental symptoms and musculoskeletal disease. Among the work stressors, high physical demands at work, poor physical work environment, and lack of freedom were associated with impaired work ability. Muscular work, disturbing temperatures at the workplace, and lack of freedom particularly affected employees with disease, whereas poor work postures and role conflicts at work were particularly injurious for healthy employees. The worst situation was observed when a worker with many symptoms and disease was exposed to many different work stressors. Life satisfaction, sitting work posture, a good basic education, and physical exercise during leisure time were associated with good work ability.

Cardiovascular Diseases↗
PubMed1991

Summary and recommendations of a project involving cross-sectional and follow-up studies on the aging worker in Finnish municipal occupations (1981-1985).

This report is a summary of the main findings of 15 studies comprising a multidisciplinary research project. Recommendations are also made on the basis of the findings, and they emphasize the following points: (i) work demands should change with age, (ii) work should be designed for unhealthy people, (iii) work ability should be promoted, (iv) work ability should be regularly monitored, (v) special attention to stress reactions is needed, (vi) knowledge of aging is needed, and (vii) action programs are needed.

Aging↗
PubMed1991

Mortality, disability and changes in occupation among aging municipal employees.

During a four-year follow-up period the indicators of work load, individual factors, and stress reactions predicting mortality, disability, and change of occupation were studied. In 1981, 6257 active workers aged 44-58 years answered a questionnaire. The study was repeated in 1985 when 1% of the subjects had died, 9% had become disabled, and 5% had changed their occupation. These changes had occurred the most often in occupations which included muscular work, poor work postures, and a poor physical environment. The highest mortality rate was observed for the male installation and auxiliary workers who had reported the presence of cardiovascular, but no musculoskeletal, disease four years earlier. The highest disability rate was well predicted by a poor index of work ability. Major diseases leading to disability included malignant tumor, coronary artery disease, congestive heart failure, rheumatoid arthritis, bronchitis or bronchial asthma, and mental disease. Work-related stress reactions were associated with both mortality and disability.

Cardiovascular Diseases↗
PubMed1991

Prevalence and incidence rates of diseases and work ability in different work categories of municipal occupations.

The purpose of this study was to determine the relationship between the health status and work ability of individuals representing a variety of municipal occupations. In both 1981 and 1985, 4255 employees answered a postal questionnaire. The subjects, aged 44-58 years in 1981, were grouped into physical, mental, or mixed physical and mental job categories. Occupational groups with a high disease prevalence in 1981 had a high, and occupational groups with a low disease prevalence in 1981 a low, disease incidence during the follow-up period. In 1985 every second subject suffered from a musculoskeletal disease. The highest disease prevalence was observed for physically demanding occupations and for men in work with mixed physical and mental demands. Female auxiliary workers, domestic helpers and cooks, and also male installation and transport workers, had the poorest health. The men and women in mental work had the best health and work ability.

Cohort Studies↗
PubMed1991

Background and objectives of the Finnish research project on aging workers in municipal occupations.

In Finland, the proportion of 45- to 64-year-old people in the work force is expected to increase from 31.1 to 40.1% between 1980 and 2000. A multidisciplinary study was carried out to test the factors of work, health, work ability, functional capacity, and perceived strain as criteria for determining new concepts for retirement age. The first phase of the project comprised cross-sectional studies in which the age of the 6257 working subjects ranged from 45 to 58 years. The second phase covered a four-year follow-up of these same subjects. The main results of the 15 various studies are given in separate articles. Recommendations for improving the work and promoting the work ability of the aging worker have been made on the basis of the findings of the project.

Aged↗
PubMed1991

Effect of retirement on health and work ability among municipal employees.

A questionnaire was sent to 6257 active employees, mean age 50.5 years, in 1981, and again in 1985, when 4255 of the workers were still actively working, 402 had retired because of age, and 468 had retired for medical reasons. After retirement, regardless of reason or previous work content, the prevalence of musculoskeletal diseases changed little among the women but increased markedly among the men retired from mental work. Among the men retired from mental work because of age, the prevalence of cardiovascular diseases increased after retirement. After disability pensioning the prevalence of cardiovascular diseases increased for both the men and the women. The prevalence of poor work ability increased in all the work categories irrespective of the type of retirement. Work ability did not improve after old-age pensioning, but health status was improved among the men and women in some occupational groups. Therefore light, part-time work should not be excluded for retired people.

Cardiovascular Diseases↗